Biological fluid filters having flexible walls and methods for making such filters

ABSTRACT

Flexible housing filters for filtration of fluids and methods of making such filters are disclosed. The filters may include one or more peripheral seals in the flexible housing.

FIELD OF THE DISCLOSURE

The present disclosure is directed to filters for the filtration offluids such as, but not limited to, biological fluids and to methods ofmaking such filters wherein at least the walls of the housing are madeof a flexible material. More particularly, the present disclosure isdirected to flexible housing filters that include one or more peripheralseals or, in the alternative, include a molded frame with flexible wallsthat capture the filter medium with no peripheral seals.

BACKGROUND

Using various manual and automated systems and methods, whole blood iscollected and separated into its clinical components (typically redblood cells, platelets, and plasma). The collected components aretypically individually stored and used to treat a variety of specificconditions and diseased states.

Before transfusing the collected blood components to a recipient in needof the components, or before subjecting blood components to furthertreatment, it is often desirable to minimize the presence of impuritiesor other materials that may cause undesired side effects in therecipient. For example, because of possible reactions, it is generallyconsidered desirable to reduce the number of leukocytes in bloodcomponents before storage, or at least before transfusion (i.e.,“leukoreduction”).

Filters are widely used to accomplish leukoreduction in blood productstoday (e.g., filtration of leukocytes from whole blood, red cells,and/or platelet products). Filters typically include a filter mediadisposed between mating and/or opposed walls of a filter housing. Inletand outlet ports associated with the housing provide flow to and fromthe interior of the filter. Traditionally, the walls of the filterhousing have been made of a rigid, typically polymeric, material. Morerecently, filters wherein at least the walls of the housing are made ofa flexible material have been used in blood collection kits. Soft orflexible housing filters provide the advantage of being able towithstand handling and centrifuging without breakage of the filter.Examples of soft housing filters are disclosed in U.S. Pat. No.6,367,634; U.S. Pat. No. 6,422,397; U.S. Pat. No. 6,745,902; U.S. Pat.No. 7,353,956; U.S. Pat. No. 7,332,096; U.S. Pat. No. 7,278,541; andU.S. Patent Application Publication No. 2003/0209479, all of which arehereby incorporated by reference herein.

While flexible housing filters are now commonly used in the field ofblood processing, there exists an ongoing desire to improve theconstruction, performance, and manufacturability of such filters.

SUMMARY

In one aspect, the present disclosure is directed to a biological fluidfilter assembly including a housing having first and second flexiblewalls wherein one of the walls includes an inlet port and the other wallincludes an outlet port. The filter assembly includes a filter mediumdisposed between the flexible housing walls. The filter medium includesat least first, second and third elements wherein the first element ismade of or includes a material suitable for removing a component orparticulate of a biological fluid and is disposed between the inlethousing wall and the second element; the second element may be made ofor include a material suitable for removing another component of saidbiological fluid and is disposed between the first element and the thirdelement; and the third element is made of an organic or inorganicmaterial and is disposed between the outlet housing wall and the saidsecond filter element. The third filter element has a thickness of lessthan 0.04 cm or greater than 0.25 cm. The filter assembly includes anouter peripheral seal and at least one inner peripheral seal spacedinwardly from the outer peripheral seal.

In another aspect, the present disclosure is directed to a biologicalfluid filter assembly including a housing having first and secondflexible walls wherein one of the walls includes an inlet port and theother wall includes an outlet port. The filter assembly includes afilter medium disposed between the flexible housing walls. The filtermedium includes at least first, second and third elements wherein thefirst element is made of or includes a material suitable for removing acomponent or particulate of a biological fluid and is disposed betweenthe inlet housing wall and the second element; the second element may bemade of or include a material suitable for removing another component ofsaid biological fluid and is disposed between the first element and thethird element; and the third element is made of an organic or inorganicmaterial and is disposed between the outlet housing wall and the secondfilter element. The third filter element has a gas permeability per 1 cmof thickness of greater than 40 cm²/s.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a plan view of a flexible housing filter assembly inaccordance with the present disclosure;

FIG. 2 is a side view of the flexible housing filter of FIG. 1;

FIG. 3 is a cross-sectional end view taken along line 3-3 of theflexible housing filter of FIG. 1;

FIG. 4 is an exploded view of a filter assembly in accordance with thepresent disclosure;

FIG. 5 is an enlarged cross-sectional view of an inner peripheral sealregion of the filter assembly shown in FIGS. 1-4;

FIG. 6 is plan view of another embodiment of a flexible housing filterassembly in accordance with the present disclosure;

FIG. 7 is a cross-sectional end view taken along line 7-7 of theflexible housing filter of FIG. 6;

FIG. 8 is an enlarged cross-sectional view of the dual inner peripheralseal regions of the filter assembly shown in FIGS. 6-7;

FIG. 9 is plan view of still another embodiment of a flexible housingfilter assembly in accordance with the present disclosure;

FIG. 10 is a cross-sectional end view taken along line 10-10 of theflexible housing filter assembly of FIG. 9;

FIG. 11 is a partial, cross-sectional view of the outer peripheral sealof the filter assembly of FIGS. 9-10;

FIG. 12 is a partial an enlarged cross-sectional view of an inner sealregion of the filter assembly shown in FIGS. 9-10;

FIG. 13 is a plan view of one embodiment of the third element of thefilter assembly of any one of the previous embodiments;

FIG. 14 is an exploded view of the housing walls and first, second andthird filter elements including the third element of FIG. 13;

FIG. 15 is a partial, cross-sectional view of an inner peripheral sealof the embodiment of the filter assembly of FIGS. 13-14;

FIG. 16 is an exploded view of the housing walls, first, second andthird filter elements and an alternative embodiment of the third elementof FIGS. 13-14;

FIG. 17 is a cross-sectional end view of a filter assembly including theembodiment of the third element as shown in FIG. 16;

FIG. 18 is plan view of another embodiment of a filter assembly inaccordance with the present disclosure;

FIG. 19 side view of the filter assembly of FIG. 18;

FIG. 20 is a perspective view of the filter assembly of FIGS. 18-19;

FIG. 21 is a further perspective view of the filter assembly of FIGS.18-19 with a portion of a flexible housing wall and a portion of themolded frame broken away;

FIG. 22 is a perspective view of the filter stack (of filter mediasheets) in the filter assembly of FIGS. 18-19;

FIG. 23 is a perspective view of the filter assembly of FIGS. 18-20prior to attachment of the flexible outlet and inlet housing walls;

FIG. 24 is a perspective view of still another embodiment of a filterassembly in accordance with the present disclosure;

FIG. 25 is a partial view of the filter assembly of FIG. 24 with a portin the molded frame;

FIG. 26 is a top, plan view of the filter assembly of FIGS. 24-25;

FIG. 27 is an end view of the embodiment of the filter assembly of FIGS.24-26;

FIG. 28 is an end view of an alternative embodiment of the filterassemblies of FIGS. 18-26; and

FIG. 29 (a)-(e) depicts the steps in a method of making a filterassembly in accordance with the present disclosure.

DETAILED DESCRIPTION OF THE EMBODIMENTS

The present disclosure is directed to a filter assembly 10 useful in theremoval of selected components or compounds from a biological fluid,such as blood. As shown in FIGS. 1 and 2 and in accordance with thepresent disclosure, filter assembly 10 includes a housing 12 defined bya pair of outer housing walls 14 and 16. In one embodiment, housingwalls 14 and 16 of housing 12 may be separate sheets of a flexiblematerial such as, but not limited to, polyvinyl chloride or any othersuitable material through which the biological fluid will not flow. Theseparate sheets may be sealed together along their peripheries as willbe described in greater detail below. Alternatively, walls 14 and 16 maybe provided from a single sheet of suitable flexible material foldedover itself and sealed along the non-folded sides and/or end(s) of thefacing panels. Still further, housing 12 may be provided as a pocket,sealed along three sides and open along one side through which thefilter medium may be introduced, followed by the sealing of theremaining open end.

As shown in FIGS. 1 and 2, “inlet” housing wall 14 and “outlet” housingwall 16 include inlet port 18 and outlet port 20, respectively,positioned on opposite sides and near opposite ends of filter assembly.Ports 18 and 20 need not be located near opposite ends of the filterassembly 10 but may be positioned elsewhere, such as more centrallylocated and directly opposite each other. Ports 18 and 20 are adapted toreceive other components of the fluid processing set such as tubing orthe like. Inlet and outlet ports 18 and 20 may be secured to theassociated walls 14 and 16 by any suitable means (e.g., being heatsealed thereto using radio frequency energy), or may be integrallymolded with housing walls 14 and 16 as described in InternationalPublication WO 00/62891, the contents of which are incorporated hereinby reference. Walls 14 and 16 of the filter housing 12 are eachpreferably provided with an opening/aperture and an internal flow path(not shown) through which fluid flows into and out of filter assembly10.

As further shown in FIGS. 1 and 2, housing walls 14 and 16 are joinedtogether at least substantially around their peripheries to form housing12, and preferably entirely around their peripheries. In one embodiment,housing walls 14 and 16 are joined at their outermost peripheries withan outer peripheral seal 22. In addition, in accordance with the presentdisclosure, housing 12 may also include one or more “inner peripheralseals” 24 (and 26, as shown in FIGS. 6-8) spaced inwardly from outerperipheral seal 22. A gap 28 between outer peripheral seal 22 and innerseal 24 (or outer seal 22 and inner seals 24 and 26) provide(s) acushioned periphery of the type described in U.S. Patent Publication No.2003/0209479, which is incorporated by reference herein in its entirety.

In one embodiment shown in FIG. 1, both outer seal 22 and inner seal 24may have an at least substantially uniform width of greater than 6 mmand more preferably a width of between approximately 6-12, 6-10, or 6-8mm. Gap 28 between outer 22 and inner 24 seals of FIG. 1 may beapproximately 1-10, 1-8 or 1-6 mm. In the embodiment of FIG. 6, innerseal 24 may have a width of approximately 0.5-7, 0.7-5 or 1.0-4 mm.Outer seal 22 may have a width of greater than approximately 6 mm andmore particularly approximately 6-12, 6-10 and 6-8 mm. Gap 28 and 28′between each of the adjacent seals may have a width of approximately1-10, 1-8 or 1-6 mm.

With respect to the embodiment of FIG. 9 (discussed in more detailbelow) inner seal 24 may have a seal width of approximately 0.5-7,0.7-5, 1.0-4 mm and outer seal 22 may have a seal width of greater than6 mm and more particularly 6-12, 6-10 or 6-8 mm. Gap 28 between theinner and outer seals may have a width of approximately 1-10, 1-8 and1-6 mm.

As shown in FIGS. 3-4, 7, 10, 14-16 filter assemblies of the typedisclosed herein further include a filter medium 30 that is capturedbetween housing walls 14 and 16. Filter medium 30 may include one ormore sheets of one or more materials capable of removing selectedcomponents, compounds, or other particulates from the biological fluid.In one embodiment, filter medium 30 is specifically suited for theremoval of at least leukocytes from blood. The one or more sheets offilter material may be made of any suitable biocompatible, medical gradematerial with pores sized to remove the selected components, compoundsor other particulates. The one or more sheets of filter medium may beprovided as a mesh, a woven fiber, a melt-blown, non-woven fibrousmaterial or other suitable porous structure.

In one embodiment, filter medium 30 may include a plurality of sheets,such as, for example, a plurality of melt-blown, non-woven fibroussheets. In a further embodiment, filter medium 30 may be provided as apad or stack of a plurality of filter sheets, as shown in FIG. 3 andmore particularly, in FIG. 4.

As shown in FIG. 4, a filter pad or stack of filter medium 30 mayinclude a plurality of individual sheets, one or more of which define atleast first, second and third elements or regions that are suited forthe selective removal of components, or compounds, or particulatesand/or to provide other functions to filter assembly 10. For example, asshown in FIG. 4, filter medium 30 may include at least a first elementor region 32, a second element or region 34, and a third element orregion 36. The stack of sheets that includes elements 32, 34, 36 iscaptured between housing walls 14 and 16 and sealed in the mannerdescribed above.

Thus, for example, as further shown in FIG. 4, first element or region32 may preferably be adjacent to inlet housing wall 14. Although shownas a single sheet in FIG. 4, it will be understood that the firstelement or region 32 may include one or more sheets of a selectedfiltration material. The first element may be referred to as“pre-filter” and may be particularly well suited for the removal ofmicroaggregates.

Continuing with a description of the elements or regions that make upfilter medium 30 in the direction of flow from the inlet housing wall 14toward the outlet housing wall 16, a second element or region 34 islocated downstream of first element 32. As shown in FIG. 4, secondelement 34 may include one or more sheets of a filter material of thetype described above that is capable of removing certain bloodcomponents, such as leukocytes. Typically, element 34 may include aplurality of sheets, most typically between 2 and 50 individual sheetseach preferably made of a melt-blown, non-woven fibrous material.Continuing in the downstream direction from second element 34 is a thirdelement 36 that is located between the second element and the adjacentoutlet housing wall 16. The first, second and third elements 32, 34 and36 will now be described in greater detail.

As noted above, first element 32 may be considered a “pre-filter” forfiltering out certain larger-sized particles and components. Element 32is preferably made of any suitable biocompatible material with poressufficiently sized to remove or retain certain particles, such asmicroaggregates, while allowing other components, such as leukocytes, tosubstantially pass. In one embodiment, the material(s) used for thesheet(s) that make up first element or region 32 may bepolybutyleneterephthalate (PBT), polyethyleneterephthalate (PET), orpolypropylene. In an embodiment, the overall thickness of first element32 (in the unsealed areas of filter medium 30) may be approximately0.127-1.106 mm. More particularly, the thickness of first element 32 maybe approximately 0.305-0.711 mm and even more particularly approximately0.432-0.559 mm.

Second element or region 34 may provide the filtration region of filtermedium 30 that is primarily responsible for the removal of blood cells.Thus, second element 34 may typically be made of a biocompatiblematerial with pores sized to retain leukocytes, i.e., white blood cells.Materials suitable for use as the second element 34 include the PBT, PETand PP materials described above in connection with first element 32.Second element 34 may have a thickness in the unsealed areas of themedium of approximately 0.254-15.24 mm, or more particularly,approximately 5.08-12.7 mm, and even more particularly approximately7.11-8.9 mm.

Third element or region 36 (sometimes referred to as the “post-filter”)may likewise be made of a suitable biocompatible porous material thatallows for the filtrate to pass and exit through outlet port 20 inoutlet housing wall 16. Third element 36 may further serve as a manifoldor support and spacing structure between housing wall 16 and filtermedium 30. Third element 36 may be made of any organic or inorganicmaterial and may be a mesh, a woven fibrous structure, or a melt-blown,non-woven fibrous structure. In a preferred embodiment, third element 36has a (gas) permeability per 1 cm of thickness of greater than 40 cm²/s.The thickness of third element 36 in the unsealed areas of filter medium30 is preferably less than 0.04 cm or greater than 0.25 cm. In oneembodiment, third element 36 may be a sheet that includes a meshinterior and, optionally, a non-mesh frame, as shown in FIG. 13 anddescribed in greater detail below.

As discussed above and shown in FIGS. 1-12, filter assembly 10 and morespecifically housing 12 of filter assembly 10 includes an outerperipheral seal 22 and one or more inner seals 24 (and, optionally, 26)inwardly spaced from outer peripheral seal 22. Both inner and outerseals 24 and 26 may be formed by any suitable means, such as pressureapplication, heat sealing and, preferably, radio frequency (RF) sealing.

In one embodiment, outer seal 22 may be formed strictly between theopposing housing walls 14 and 16. Inner seal 24, on the other hand,captures both housing walls 14 and 16 and the intervening elements orregions 32, 34 and 36 of filter medium 30 and the sheets thereof, asshown in FIGS. 5, 8 and 12. Thus, for example, inner seal 24 may includethe housing material of housing walls 14, 16 and some or all of first,second and third elements described above. Where more than threeelements are included in filter medium 30, inner seal 24 may likewiseinclude material of some or all of such additional elements. Seals 22and 24 (and 26) may be formed in a sequential process or in asimultaneous process. In addition, the elements of filter medium 30 maybe sealed together first, followed by the sealing of housing walls 14and 16 to the filter medium in a two-step process. Alternatively, thehousing walls and filter medium 30 may be sealed altogether in aone-step process.

In accordance with the present disclosure, as a result of the appliedpressure and RF energy, inner and outer seals 24, 26 and 22 definecompressed areas that may include one or more differentiated orundifferentiated layers or bands within the seal. It will be understoodthat the inner seals 24 and/or 26 may themselves include a centralsection 38 of substantially uniform thickness between flared and lesscompressed peripheral sections 41, as shown in FIGS. 5, 8, 12 and 15.The thickness of the inner seals 24 and/or 26 and of the layers or bandswithin such seals described below are preferably an average of anywherebetween 4-10 measurements taken within the central section 38 of theseal, as shown in FIGS. 5, 8 and 12, for example. Thus, in oneembodiment, inner seals 24 and/or 26 may have a thickness ofapproximately 0.762-2.286 mm, more preferably approximately 1.02-2.032mm and even more preferably approximately 1.27-1.778 mm.

In one embodiment, where housing walls 14 and 16 are sealed directly toeach other at the outermost periphery, i.e., such outer seal 22 includesa single region 35 made up entirely of the material (for example, PVC)of housing walls 14 and 16. Inasmuch as inner seals 24 and/or 26 mayinclude filter elements 32, 34 and 36, such inner seals 24 and 26 mayinclude several layers or bands made up of the outer housing materials,materials of the filter medium 30 including the material of first,second and/or third filter elements, and composites or commingled layersthereof. Thus, in an embodiment where inner seal 24 and/or 26 includesthe material(s) of the inner and outer housing wall 14 and 16 and thethree filter elements 32, 34 and 36 (described above and shown in FIGS.5, 8 and 12), seal 24 and/or 26 may include, in the direction of flow, afirst layer 37 that includes entirely or at least substantially entirelythe material of inlet housing wall 14. Using a scanning electronmicroscope, the post-seal thickness of such band 37 of the housing wall14 may be approximately 0.076-0.381 mm or more particularlyapproximately 0.127-0.304 mm, or even more particularly 0.178-0.250 mm.

Adjacent to the first layer or band 37 and downstream therefrom is asecond layer 44 that may be a composite of the housing material and thefirst and second elements or regions 32 and 34, described above andshown in FIG. 4. Composite layer 44 may have a post-seal thickness ofapproximately 0.1-0.5 mm, more particularly approximately 0.1-0.35 mmand even more particularly approximately 0.1-0.2 mm.

Downstream of layer 44 is preferably layer or band 46, which at leastsubstantially includes the material of element 34 (i.e., the material(s)of the filter medium 30 for removing leukocytes). In accordance with thepresent disclosure, layer 46 may have a post-seal thickness ofapproximately 0.508-1.27 mm or more particularly approximately0.635-1.143 mm, or even more particularly approximately 0.762-0.9 mm.

Continuing with a description of the layers or bands within inner seals24 and/or 26 (as measured within central section 38) and proceeding inthe direction of flow and downstream of region 46 is region 48, whichmay be a composite of the material of housing wall and third filterelement 36. The post seal thickness of layer 48 is less than 0.15 mm andmore particularly approximately 0.001-0.12 mm and 0.01-0.08 mm. Finally,as further shown in FIGS. 5 and 8, layer 39 may include entirely or atleast substantially entirely the material of outlet housing wall 16. Thepost-seal thickness of layer 39 may be approximately 0.254-0.406 mm,more particularly approximately 0.304-0.381 mm or approximately0.330-0.3556 mm.

As described above, outer seal 22 may simply consist of the housingmaterial of inlet and outlet walls 14, 16. In another embodiment, shownin FIGS. 9-12, outer seal 22 may also capture at least the first andsecond elements 32 and 34, respectively, as shown in FIG. 11. Thus,outer seal 22 includes, in the direction of flow, layers made up of theessentially housing material only having a thickness of approximately0.076-0.381 mm, more particularly 0.127-0.304 mm, and even moreparticularly 0.178-0.25 mm. Following this region, there is a compositelayer 22′ that includes the housing material and the first and secondregions, wherein the post-seal thickness of this composite layer isbetween approximately 0.076-0.762 mm, more particularly between0.127-0.508 mm, and even more particularly between 0.178-0.381 mm. An RFdie that includes a tear seal feature that also cuts and separates thenow sealed filter assembly from the flexible housing sheets and filtermedia may be used. A smart generator may be particularly well-suited forsuch outer seal operation. (The thicknesses of the bands or layerswithin central section of inner seals 24 and/or 26 may be substantiallyas previously described above.)

In another embodiment, as shown in FIGS. 13-17, the third element 36′may be a sheet with a central porous region 40, such as a mesh and anouter peripheral frame 42 integral with central porous region 40. Asshown in FIG. 15, frame 42 or at least a portion of frame 42 may becaptured within inner seal 24 and/or 26. In a further alternative, themesh may be provided without a frame, wherein the peripheral portions ofthe all-mesh sheet may be captured within inner seal 24 and/or 26. In afurther alternative, as depicted in FIG. 16, where the third element 36″is an all-mesh sheet without a frame, no part of the this third elementis captured by inner seal 24 and/or 26. In this embodiment, thirdelement or region 36″ may be “free-floating” within filter assembly 10.

The material of the third element 36′, 36″ defines openings or voidsthrough which filtered fluid passes before exiting the filter assembly10 via the outlet port 20. The third element 36′ (or 36″) of FIG. 13 isshown with generally diamond-shaped openings or voids, but it is withinthe scope of the present disclosure for the openings or voids to bedifferently shaped (e.g., a regular shape, such as generally square orrectangular or circular or triangular or pentagonal or hexagonal, or anirregular shape). A primary purpose of the third element 36′, 36″ may beto act as a manifold which separates the filtration medium 34′, 34″ fromthe outlet side 16 of the filter housing, while allowing filtered fluidto freely flow from the filtration medium 34′, 34″ to outlet port 20.Accordingly, the voids in porous region 40 may be relatively large toprovide third element 36′, 36″ with a porosity that is greater than theporosity of the filtration medium 34′, 34″. However, if the voids aretoo large, it is possible for the outlet side 14 of the filter housingto press against the filtration medium 34′, 34″ during use, therebymaking it more difficult for filtered fluid to flow out of the filterassembly 10. Thus, it may be preferred for the third element 36′, 36″ tohave an intermediate porosity, with voids that are large enough to allowsubstantially free flow of filtered fluid out of the filter assembly 10,but not so large as to negate the desired manifold effect. In oneexemplary embodiment, the voids are generally rectangular or square ordiamond-shaped, each having a height and width in the range ofapproximately 0.5-20 mm, with the third element 36′, 36″ having athickness in the range of approximately 0.5-4 mm.

Alternatively, rather than characterizing the porosity of the thirdelement 36 (and more particularly porous region 40) in terms of the sizeand shape of its voids, it is also possible to characterize its porosityin terms of its permeability properties. For example, at a pressuredifference of 250 Pa (2500 dyne/cm²), the porous region 40 of thirdelement 36′, 36″ may have a Frazier (air) permeability of approximately899 cm³/s·cm² (which is a raw value for the mesh of the third element36′, 36″ having a thickness of approximately 1.6 mm, which may benormalized to approximately 143.8 cm²/S for a third element 36′, 36″having a thickness of 1 cm) or an air permeability in the range ofapproximately 800 cm³/s·cm²-2000 cm³/s·cm² (which is a range of rawvalues for the mesh of the third element 36′, 36″ having a thickness ofapproximately 1.6 mm, which may be normalized to a range ofapproximately 40 cm²/s-800 cm²/s for the mesh of the third element 36′,36″ having a thickness of approximately 1 cm), but it is also within thescope of the present disclosure for the third element 36′, 36″ to havean air permeability that lies outside of this range.

The permeability of third element 36′, 36″ may also be characterized interms of its permeability properties using Darcy's law. According toDarcy's law, the velocity of flow through a porous medium may beexpressed by the following equation: ν=−k/μ∇P, in which v is velocity, kis the permeability of the medium (also referred to as the Darcy's lawconstant), μ is the dynamic viscosity, and ∇P is the pressure gradient.

In one embodiment, in which the porous region 40 of third element 36′,36″ has a permeability of approximately 899 cm³/s·cm² at a thickness of1.6 mm, at a pressure difference of 250 Pa (2500 dyne/cm²), the Darcy'slaw constant of the mesh of the third element 36′, 36″ was determined tobe approximately 1052 μm². In another embodiment, the Darcy's lawconstant of the third element 36′, 36″ may be in the range of 293 toapproximately 5852 μm², but it is also within the scope of the presentdisclosure for the mesh of the third element 36′, 36″ to have a Darcy'slaw constant that lies outside of this range.

The porous region 40 of third element 36′, 36″ may have a generallyuniform porosity or permeability, with generally uniform voids arrangedin a uniform pattern, or may have a non-uniform porosity orpermeability, with differently sized and/or shaped voids in a uniform ornon-uniform pattern or generally uniform voids arranged in a non-uniformpattern.

As in the embodiments described above, inner seal 24 of the embodimentof FIG. 15 may include layers or bands made up of the outer housingmaterials, materials of the filter medium 30 including the materials ofthe first, second and third filter elements and/or composites thereof.Thus, as shown in FIG. 15, inner seal 24 may include, in the directionof flow, a first layer 37′ made up at least substantially entirely ofthe inlet housing material, such as polyvinyl chloride. Downstream oflayer 37′ is a second layer 44′ that may be a composite of the housingmaterial and the first and possibly also the second elements or regions32′ and 34′ (see FIG. 14). Downstream of layer 44′ is preferably a layeror band 46′ which at least substantially includes the material of filterelement 34′, i.e., the material(s) of the filter medium for removingleukocytes.

Next, the seal region may include a band or layer 48′ which may be acomposite of the material of the third filter element 36′, 36″ (and/orframe 42 thereof) the material of the outer housing wall 16, if thematerial of the third element is different from the material of thehousing wall. Composite layer 48′ may be followed by and adjacent to alayer 39′ that includes primary or at least substantially the materialof outer housing wall 16.

In an embodiment, such as for example, where the third filter element isa mesh (with or without a frame region) as described in connection withFIGS. 13-17, the material of the third element may be identical to thematerial of the outer housing wall (e.g., polyvinyl chloride). In thisembodiment, the seal may be devoid of composite layer made up of thethird filter element and outer housing wall 16. In this embodiment, thedownstream most layer or band may be present as an undifferentiatedlayer, band or region or aggregate of the common material. In oneembodiment, a (molten) layer 46′ of the second filter element 34′ may beat least substantially excluded from central region 38′ of inner seal 24(and 26) such that a more downstream layer (e.g., the thirdelement/outlet housing commingled layer), band or region may be adjacentto the upstream composite layer 44′ described above in at least centralsection 38′. In one embodiment, this may be achieved by a sealingprocess in which the commingled and typically undifferentiated layer orregion at least substantially displaces the layer of molten main filtermaterial 46′ toward and into peripheral sections 41. A more detaileddiscussion of a seal utilizing a mesh element of the type describedabove, the characteristics of the bands or layers within the inner seal,and methods for forming such a seal are set forth in a simultaneouslyfiled U.S. patent application identified by docket number F-6675(9560-0002) in the names of Paolo Verri et al., the contents of whichare incorporated by reference herein.

FIG. 18 shows an alternative embodiment of a filter assembly 50 inaccordance with the present disclosure. As shown in FIGS. 18-21, filterassembly 50 includes a frame 52 that houses filter medium 60, describedin greater detail below. Frame 52 includes a rim 53 that defines centralopening 55 with walls 54 and 56 located at the inlet side and the outletside of filter assembly (as defined by the placement of the inlet andoutlet ports described below). Frame 42 and, for that matter, rim 53 andcentral opening 55, may be rectangularly-shaped, but may also have othershapes such as a square, circle, oval, triangle, diamond, etc. Walls 54and 56 may be made of any flexible medical grade polymeric material thatis impermeable to liquid including, but not limited to, plasticizedpolyvinyl chloride (PVC).

As in the previous embodiments described above, walls 54 and 56 maycarry inlet and outlet ports 57 and 58, respectively. Ports 57 and 58define flow paths 59 that allow liquid introduction into and liquidwithdrawal from filter assembly 50.

Filtration medium 60 (FIGS. 21-22) may be provided as a stack or pad ofselectively porous sheets substantially as described above in connectionwith the earlier embodiments of FIG. 1-17. Thus, filter medium 60 mayinclude at least first and second regions such as a first (pre-filter)element and a second (main filter) element. A third filter element 36may optionally be included, but more preferably is not included. In analternative embodiment, frame 52 may be molded with ribs to space filtermedium 60 from outlet housing wall 56. Materials suitable for thedifferent elements include, but are not limited to PBT, PET and PP andthe thicknesses of the sheets or plurality of sheets may be aspreviously described.

Unlike the embodiments of FIGS. 1-17, the filter assembly of FIG. 18does not require and typically does not include internal seals (24and/or 26), although some joining of the filter elements by welding oradhesion may be employed. Accordingly, filter assembly 50 does not havelayers or bands within a seal that includes composites of two or morematerials, or a cushioned periphery. With a molded frame, filterassembly would likewise not include an outer peripheral seal of flexiblehousing walls 54 and 56.

In accordance with the present disclosure, frame 52 may be molded suchas by injection molding. More particularly, frame 52 may be insertmolded such that the outer edges of the filter medium 60 pad or stack(and in the embodiment described in the preceding paragraph, theflexible housing walls) are contained and captured within the frame, asshown for example in FIG. 21. Frame 52 may be molded from any suitablepolymeric material. In one embodiment, frame 52 may be molded frompolyvinyl chloride (PVC). Other suitable materials include polyester,hytrel and other material suitable for RF or thermal induced welding.Flexible walls 54 and 56 may be attached to frame 52, preferably alongthe entirety of rim 53 of both the front and rear of frame 52, i.e., atthe inlet side and the outlet side of frame 52. As shown in FIG. 23,ports may be pre-attached to flexible walls 54 and 56.

In a another alternative, rather than sealing flexible housing walls 54and 56 to frame 52 and over central opening 55, flexible housing walls54 and 56 may be “stacked” and joined with the sheets of the filtermedium 60 around which frame 52 is molded. Thus, flexible housing 52 and54 with or without ports 57 and 58 are captured with filter medium 60 bythe molded frame 52.

Also, in an alternative embodiment of filter assembly 50′, shown inFIGS. 24-28, ports 57′ and 58′ may be integral with frame 52′ and notpre-attached to walls 54 and 56. More particularly, ports 57′ and 58′may be integrally formed (i.e., molded) with frame 52′. Thus ports 57′and 58′ shown in FIGS. 24-28 define flow paths 59′ through frame 52.Ports 57′ and 58′ define apertures at opposing ends 62 and 64 of frame52′ for connection or attachment with tubing of a blood collection set.Flexible walls 52 and 54 are attached to the outer surface of frame 52′along rim 53′ or, alternatively may be pre-assembled with filter mediumand captured by frame 52 during the insert molding process, as describedabove.

As shown in FIG. 29, filter assembly 50 (or 50′) may be assembled asfollows. A sheet 66 of multi-layered filter media 60 is provided andsegmented into individual, smaller-sized pads 60. Pads 60 may besegmented by cutting, as seen in FIG. 29( b). Individual pads 60 maythen be inserted into a mold 61 for molding with an injected moltenpolymer (See FIG. 29( c)). Once the molded frame has cooled, filtersubassembly 50 is removed from the mold. Flexible housing sheets 54 and56 (with or without pre-attached inlet and outlet ports 57 and 58) maythen be attached to frame 52′. Alternatively, flexible housing sheets 54and 56 may be joined to the filter stack prior to molding of the frame.It will be appreciated that frame 52 may include integrally molded portsas shown in FIGS. 25-28, in which case flexible housing sheets would notinclude pre-attached ports.

Examples

Without limiting any of the foregoing, the subject matter describedherein may be found in one or more apparatus. For example, in a firstaspect of the present subject matter, a biological fluid filter assemblyis set forth. The assembly includes a housing having first and secondflexible walls wherein one of the walls includes an inlet port and theother wall includes an outlet port. The filter assembly includes afilter medium disposed between said flexible housing walls. The filtermedium includes at least first, second and third elements wherein thefirst element is made of or includes a material suitable for removing acomponent of a biological fluid and is disposed between said housingwall that includes inlet port and the second element; the second elementmay be made of or include a material suitable for removing anothercomponent of said biological fluid and is disposed between the firstelement and the third element; and the third element is made of anorganic or inorganic material and is disposed between a housing wallthat includes outlet port and said second filter element. The thirdfilter element has a thickness of less than 0.04 cm or greater than 0.25cm. The filter assembly includes an outer peripheral seal and at leastone inner peripheral seal spaced from the outer peripheral seal.

A second aspect of the present subject matter includes theabove-described assembly wherein the third element has a permeabilityper 1 cm of thickness of greater than 40 cm²/s.

A third aspect of the present subject matter includes a filter assemblyin accordance with any one of the first or second aspects describedabove wherein the outer peripheral seal comprises a seal joining onlysaid housing walls.

A fourth aspect of the present subject matter includes a filter assemblyin accordance with any one of the first or second aspects describedabove wherein the outer peripheral seal comprises a seal joining saidfirst and second housing walls and at least one of the first, second andthird elements.

A fifth aspect of the present subject matter includes a filter assemblyin accordance with any one of the first through fourth aspects describedabove including a first inner peripheral seal and a second innerperipheral seal spaced from said first inner peripheral seal.

A sixth aspect of the present subject matter includes a filter assemblyin accordance with the fifth aspect described above wherein the spacebetween the first inner peripheral seal and outer peripheral seal or thespace between first and second inner peripheral seal is 1-10 mm.

A seventh aspect of the present subject matter includes a filterassembly in accordance with any one of the first through sixth aspectswherein the inner seal includes a central section between peripheralsections.

A eighth aspect of the present subject matter includes a filter assemblyin accordance with any one of the first through seventh aspectsdescribed above wherein inner peripheral seal has a thickness ofapproximately 0.762-2.286 mm.

A ninth aspect of the present subject matter includes a filter assemblyin accordance with any one of the first through eighth aspects whereinthe third element is a sheet including a mesh.

A tenth aspect of the present subject matter includes a filter assemblyin accordance with any one of the first through ninth aspects whereinthe third filter element is a sheet including a non-porous framedefining a central mesh portion.

An eleventh aspect of the present subject matter includes a filterassembly of any one of the ninth or tenth aspects wherein the sheet ismade at least substantially of polyvinyl chloride.

A twelfth aspect of the present subject matter includes a filterassembly in accordance with any one of the first through eleventhaspects described above wherein said inner peripheral seal includes aplurality of filter layers comprising (a) a layer at least substantiallycomprised of the material of the inlet housing wall (b) a layer adjacentto region (a) and comprising a material that is a composite of thematerial of the inlet housing wall and the first and second filterelement materials (c) a layer adjacent to said regions (b) and (d)comprised of the material of the second filter element (d) a layeradjacent to layer (c) and layer (e) comprising a material that is acomposite of said material of said outlet housing wall and the thirdfilter element material and (e) a layer at least substantially comprisedof the material of the outlet housing wall.

A thirteenth aspect of the present subject matter includes a filterassembly in accordance with the twelfth aspect described above whereinthe layer (d) has a thickness of less than 0.15 mm.

A fourteenth aspect of the present subject matter includes a filterassembly in accordance with any one of the first through thirteenthaspects described above wherein the filter medium including the first,second and third filter elements comprises a plurality of stackedsheets.

A fifteenth aspect of the present subject matter includes a filterassembly in accordance with the fourth aspect wherein said outerperipheral seal includes a plurality of layers comprising (a) a layer atleast substantially comprised of the material of housing wall includingsaid inlet port (b) a layer adjacent to said region (a) and comprising amaterial that is a composite of said material of said inlet housing walland the first and second filter element materials and (c) a layer atleast substantially comprised of the material of the outlet housingwall.

A sixteenth aspect of the present subject matter includes a filterassembly in accordance with any one of the first through fifteenthaspects described above wherein the first and second filter elements aremade of a material selected from the group consisting of polybutyleneterephthalate, polyethylene terephthalate and polypropylene.

A seventeenth aspect of the present subject matter includes a filterassembly in accordance with any one of the first through eleventh andfourteenth through sixteenth aspects wherein the inner peripheral sealincludes a plurality of the filter layers including (a) a layer at leastsubstantially made of the inlet housing wall material, (b) a layeradjacent to the layer (a) that includes a composite of the inlet housingwall material and the first filter element and (c) a layer downstream oflayer (b) consisting essentially of a material of the outlet housingwall and the third filter element.

An eighteenth aspect of the present subject matter includes a filterassembly in accordance with the seventeenth aspect wherein the layer (c)material is polyvinyl chloride.

In a nineteenth aspect of the present subject matter, a biological fluidfilter assembly is set forth. The assembly includes a housing havingfirst and second flexible walls wherein one of the walls includes aninlet port and the other wall includes an outlet port. The filterassembly includes a filter medium disposed between said flexible housingwalls. The filter medium includes at least first, second and thirdelements wherein the first element is made of or includes a materialsuitable for removing a component of a biological fluid and is disposedbetween said housing wall that includes inlet port and the secondelement; the second element may be made of or include a materialsuitable for removing another component of said biological fluid and isdisposed between the first element and the third element; and the thirdelement is made of an organic or inorganic material and is disposedbetween a housing wall that includes outlet port and said second filterelement. The third filter element having a gas permeability per 1 cm ofthickness of greater than 40 cm²/s.

A twentieth aspect of the present subject matter includes the biologicalfluid filter assembly of the nineteenth aspect wherein said third filterelement has a gas permeability per 1 cm of thickness of approximately 40cm²/s-800 cm²/s.

A twenty-first aspect of the present subject matter includes thebiological fluid filter assembly of any one of the nineteenth ortwentieth aspects wherein the third filter element has a thickness ofapproximately 0.5-4 mm.

A twenty-second aspect of the present subject matter includes thebiological fluid filter assembly of any one of the nineteenth throughtwenty-first aspects wherein said the filter element includes a porousregion comprising a mesh of polyvinyl chloride.

A twenty-third aspect of the present subject matter includes thetwenty-second aspect wherein the third filter element further includes asubstantially non-porous frame surrounding said porous region.

It will be understood that the embodiments and examples described aboveare illustrative of some of the applications of the principles of thepresent subject matter. Numerous modifications may be made by thoseskilled in the art without departing from the spirit and scope of theclaimed subject matter, including those combinations of features thatare individually disclosed or claimed herein. For these reasons, thescope of the invention(s) is not limited to the above description but isas set forth in the following claims, and it is understood that claimsmay be directed to the features hereof, including as combinations offeatures that are individually disclosed or claimed herein.

1. A biological fluid filter assembly comprising: a) a housing havingfirst and second flexible housing walls wherein one of said wallscomprises an inlet housing wall associated with an inlet port and saidother of said housing walls comprises an outlet housing wall associatedwith an outlet port; b) a filter medium disposed between said flexiblewalls, said medium comprising at least first, second and third filterelements wherein (i) said first element comprises a material suitablefor removing a component or particulate of a biological fluid and isdisposed between said housing wall including said inlet port and saidsecond element; (ii) said second element comprises a material suitablefor removing another component of said biological fluid and is disposedbetween said first element and said third element; (iii) said thirdelement comprises an organic or inorganic material and is disposedbetween said housing wall associated with said outlet port and saidsecond filter element, said third filter element having a thickness ofless than 0.04 cm or greater than 0.25 cm; and c) said assembly furthercomprising an outer peripheral seal and at least one inner peripheralseal spaced from said outer peripheral seal.
 2. (canceled)
 3. Thebiological fluid filter assembly of claim 1 wherein said outerperipheral seal comprises a seal joining only said housing walls.
 4. Thebiological fluid filter assembly of claim 1 wherein said outerperipheral seal joins said first and second housing walls and at leastone of first, second and third elements.
 5. The biological fluid filterassembly of claim 1 comprising a first inner peripheral seal and asecond inner peripheral seal spaced from said first inner peripheralseal.
 6. The biological fluid filter assembly of claim 5 wherein thespace between inner peripheral seal and outer peripheral seal or thespace between first and second inner peripheral seal is 1-10 mm.
 7. Thebiological fluid filter assembly of claim 1 wherein said inner sealcomprises a central section between peripheral sections.
 8. Thebiological fluid filter assembly of claim 1 wherein said innerperipheral seal has a thickness of approximately 0.762-2.286 mm.
 9. Thebiological fluid filter assembly of claim 1 wherein said third filterelement comprises a sheet including a mesh.
 10. The biological fluidfilter assembly of claim 1 wherein said third filter element comprises asheet including a non-porous frame defining a central mesh portion. 11.The biological fluid filter assembly of claim 9 wherein said sheet ismade at least substantially of polyvinyl chloride.
 12. The biologicalfluid filter assembly of claim 1 wherein said inner peripheral sealincludes a plurality of layers comprising: a) a layer at leastsubstantially comprised of the material of said inlet housing wall; b) alayer adjacent to said region (a) and comprising a material that is acomposite of said material of said inlet housing wall and said first andsecond filter element materials; c) a layer adjacent to said layers (b)and (d) comprised of said material of said second filter element; d) alayer adjacent to said layer (c) and layer (e) comprising a materialthat is a composite of said material of said outlet housing wall andsaid third filter element material; and e) a layer at leastsubstantially comprised of the material of said outlet housing wall. 13.The biological fluid filter assembly of claim 12 wherein layer (d) has athickness of less than 0.15 mm.
 14. The biological fluid filter assemblyof claim 1 wherein said filter medium including said first, second andthird filter elements comprises a plurality of stacked sheets.
 15. Thebiological fluid filter assembly of claim 4 wherein said outerperipheral seal includes a plurality of filter layers comprising: a) alayer at least substantially comprised of the material of said inlethousing wall; b) a layer adjacent to said region (a) and comprising amaterial that is a composite of said material of a housing wall and saidfirst and second filter element materials; and c) a layer at leastsubstantially comprised of the material of said outlet housing wall. 16.The biological fluid filter assembly of claim 1 wherein said first andsecond filter elements are made of a material selected from the groupconsisting of polybutylene terephthalate, polyethylene terephthalate andpolypropylene.
 17. The biological fluid filter assembly of claim 1wherein the inner peripheral seal includes a plurality of filter layerscomprising: a) a layer at least substantially composed of the materialof said inlet housing wall; b) a layer adjacent to said region (a)comprising a composite of said material of said inlet housing wall andsaid first filter element material; and c) a layer downstream of saidlayer (b) consisting essentially of material of said outlet housing walland said third filter element.
 18. The biological fluid filter assemblyof claim 17 wherein said layer (c) comprises polyvinyl chloride. 19-21.(canceled)
 22. The biological fluid filter assembly of claim 1 whereinsaid third filter element includes a porous region comprising a mesh ofpolyvinyl chloride.
 23. The biological fluid filter assembly of claim 22wherein said third filter element further includes a substantiallynon-porous frame surrounding said porous region.